This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The Look AHEAD, multicenter, randomized controlled clinical trial will examine the impact on several health outcomes of a lifestyle intervention program designed to produce weight loss. The primary study objective is to determine whether participation in a lifestyle intervention is effective in reducing the incidence of serious cardiovascular disease events in overweight adults with type 2 diabetes. Other important study objectives are to assess the impact of weight loss and fitness changes on a range of disease processes and outcomes and to evaluate the cost-effectiveness of the weight loss intervention. The study cohort will include 5,000 overweight (body mass index of at least 25 kg/m2) individuals with type 2 diabetes (as established by self-report with verification or treatment). Sixteen centers across the United States will each recruit approximately 313 persons into the trial. Individuals with or without a prior history of cardiovascular disease will be recruited. Participants will be stratified according to center, and randomly assigned to either Lifestyle Intervention or a control intervention, Diabetes Support and Education. The Lifestyle Intervention is designed to produce and maintain weight loss and increased fitness through a lifestyle program augmented, if indicated, by subsequent use of weight loss medication. This intervention includes individual and group sessions with weekly meetings for six months followed by decreasing frequency of contact over the remainder of the trial. The Diabetes Support and Education group will receive sessions of nutrition and physical activity education and social support. Participants in both arms will receive comparable education in issues related to diabetes management. Participants in Look AHEAD will receive their general medical care from a health care provider who is separate from the Look AHEAD staff. Participants will be followed annually until 2012, resulting in a maximum of 11.5 years of participant follow-up. Outcome measures include those that might be positively affected by weight loss (e.g. cardiovascular events) and those that might be negatively affected (e.g. bone mineral density). The study will also assess some of the potential mechanisms by which weight loss may influence cardiovascular events and mortality (e.g. through improved control of cardiovascular risk factors).